Laminarin ameliorates hepatic steatosis and upregulates hepatic SMP-30 expression in high-fat-diet-induced NAFLD mice.

Senescence marker protein-30 (SMP-30; regucalcin) plays a crucial role in intracellular calcium homeostasis. This study investigated hepatic SMP-30 expression during non-alcoholic fatty liver disease (NAFLD) progression and evaluated the therapeutic potential of laminarin (LAM), a brown algae-derived polysaccharide, using high-fat diet (HFD)-fed mice and palmitic acid (PA)-treated Huh7 cells. Mice fed an HFD for 20 weeks developed NAFLD, characterized by elevated ALT/AST levels, hepatic steatosis, and significantly reduced SMP-30 expression. However, LAM treatment administered via drinking water (1%) or intraperitoneal injection (50 mg/kg) significantly attenuated lipid accumulation and restored hepatic SMP-30 expression. LAM reversed PA-induced lipid accumulation and SMP-30 downregulation in Huh7 cells. Mechanistically, LAM modulated the expression of SMP-30 and antioxidant proteins associated with activation of AKT/GSK3β/NRF2 signaling pathway, thereby mitigating the adverse effects of PA-induced toxicity. In conclusion, hepatic SMP-30 expression decreases during NAFLD progression, and LAM treatment restores these levels while alleviating lipid accumulation. These findings suggest that LAM may represent a promising therapeutic agent for NAFLD by improving lipid metabolism and reducing oxidative stress through the regulation of SMP-30.